title: Development of chimaeric West Nile virus attenuated vaccine candidate based on the Japanese encephalitis vaccine strain SA14-14-2.
abstract: Mosquito-borne flaviviruses include a large group of important human medical pathogens. Several chimaeric flaviviruses have been constructed, and show potential for vaccine development. Although Japanese encephalitis virus (JEV) live vaccine SA14-14-2 has been widely used with ideal safety and efficacy profiles, no chimaeric flavivirus based on the JEV vaccine has been described to date. Based on the reverse genetic system of the JEV vaccine SA14-14-2, a novel live chimaeric flavivirus carrying the protective antigens of West Nile virus (WNV) was constructed and recovered in this study. The resulting chimaera (ChinWNV) replicated efficiently in both mammalian and mosquito cells and possessed genetic stability after in vitro serial passaging. ChinWNV exhibited a small-plaque phenotype, and its replication was significantly restricted in mouse peripheral blood and brain compared with parental WNV. Importantly, ChinWNV was highly attenuated with regard to both neurovirulence and neuroinvasiveness in mice. Furthermore, a single ChinWNV immunization stimulated robust WNV-specific adaptive immune responses in mice, conferring significant protection against lethal WNV infection. Our results demonstrate that chimaeric flaviviruses based on the JEV vaccine can serve as a powerful platform for vaccine development, and that ChinWNV represents a potential WNV vaccine candidate that merits further development.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing 100088, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Hong-Jiang
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Shi-Hua
authors.initials: SH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Yan-Peng
authors.initials: YP
authors.lastname: Xu
authors.affiliation: Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.
authors.forename: E-De
authors.initials: ED
authors.lastname: Qin
authors.affiliation: Graduate School, Anhui Medical University, Hefei 230032, PR China.|Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.|State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China.|Graduate School, Guangxi Medical University, Guilin 530021, PR China.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D002460:Cell Line; D015195:Drug Design; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D022321:Japanese Encephalitis Vaccines; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000235:genetics / Q000276:immunology; D014902:West Nile virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology
chemical_list: D022321:Japanese Encephalitis Vaccines; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D053060:West Nile Virus Vaccines